The research proposals described in this application concern three primary aspects of myocardial ischemia. The coronary collateral circulation will be investigated to determine its role in the protection of the heart and its response to the placement of an aortic-coronary bypass graft. The studies will be performed using radioisotope labeled microspheres employing a technic which permits quantitative flow studies for segments and layers of the myocardium. Safer and simpler tests of cardiac function and localization of coronary lesions will be studied on a developmental basis for determination of cardiac output, ejection fraction, and site of coronary arterial lesions by the use of injectable radioisotopes with computer analysis. Thirdly, the ischemic electrophysiological changes which occur on the epicardium and in the intramural myocardium will be assessed in experimental preparations with myocardial insufficiency and subsequent bypass grafts. These alterations will also be assessed in the clinical situation in the operating room and postoperative period to establish the relationship of ischemic patterns on direct tracings to development of arrhythmias and hypotension. These three groups of studies are designed to elucidate more adequately the basic physiological changes which are associated with coronary insufficiency with a view toward simpler methods of diagnosis and more effective means of both pharmacologic and surgical management.